Analysis of Anticancer Activity and Chemical Sensitization Effects of Dendropanax morbifera and Commersonia bartramia Extracts.

BACKGROUND/AIM: Dendropanax morbifera (DM) and Commersonia bartramia (CB) are possible candidates for immunotherapy. In this study, the cytotoxicity and chemical sensitization of DM and CB extracts on gynecologic and colon cancers were evaluated. MATERIALS AND METHODS: The malignant cell lines were cultured and analyzed for cytotoxicity and chemical sensitization. A mouse model was also constructed to make the condition similar to in vivo. Reverse transcription-polymerase chain reaction was conducted to determine alterations in drug-resistant genes. RESULTS: The extracts from DM and CB showed specific cytotoxicity to malignant cell lines. DM increased chemical sensitivity to cervical and ovarian cancer, while CB showed improved sensitization to endometrial cancer. The effects of the extracts were confirmed using a mouse model. The extracts induced differences in the expression levels of a number of genes related to drug resistance. CONCLUSION: DM and CB extracts could be novel agents for immunotherapy and chemical sensitization in gynecologic and colon cancers.

Effect of local anesthesia on facial nerve blood flow and muscle action potential.

BACKGROUND & OBJECTIVE: The effect of direct application of local lidocaine with epinephrine on the facial nerve (FN) has not been reported. The aim of this study is to assess the effects of 2% lidocaine with 1:100,000 epinephrine at clinically relevant concentrations in a rat FN model with respect to facial nerve blood flow (FNBF) and subsequent electrophysiological changes. MATERIALS AND METHODS: To assess the influence of drugs on FNBF and electrically evoked muscle action potential (EMAP), small pieces of gelfoam were soaked in PBS 100µl (n=5, control group), 50µl (n=5, treatment group A) and 100µl (n=5, group B) of 2% lidocaine with 1:100,000 epinephrine, and 50µl (n=5, group C) and 100µl (n=5, group D) of 2% lidocaine. After 5min of stable recordings, we applied a 2% lidocaine with or without 1:100,000 epinephrine impregnated gelfoam over the main trunk of the facial nerve of rats for 30min. After removing the applied gelfoam, FNBF and threshold of EMAP were measured separately in each group. RESULTS: Compared to the control group, the treatment groups showed a significant reduction in FNBF in a dose-dependent manner. The maximal reductions in FNBF were observed in all treatment groups for a period after 10min of the application. Synergistic reduction in FNBF was greater in groups A and B than in the lidocaine applied groups (C and D). The maximal increase in the EMAP threshold was observed immediately after the respective drug application in all groups. The greatest increase in the EMAP threshold was observed in group B. The increased EMAP threshold returned to the baseline value within 120min in groups A and C. CONCLUSION: From these results, it can be considered that the topical application of lidocaine with epinephrine caused reduction in FNBF and elevation of EMAP threshold. These acute reductions in FNBF and elevations in the EMAP threshold were restored in a time-dependent manner.

ALH-L1005 attenuates endotoxin induced inner ear damage.

OBJECTIVE: To assess whether this compound (ALH-L1005) is conceivably an effective agent in protecting against cochlear damage induced by LPS. MATERIALS AND METHODS: Tube formation using human umbilical vein endothelial cell (HUVEC) and matrix metalloproteinase (MMP)-9 inhibition assay was performed. 24 guinea pigs were randomly divided into three groups. Intratympanic instillation of LPS (n=8) as negative control, instillation of oxytetracycline 1h after LPS as positive control (n=8), and intratympanic instillation of ALH-L1005 (n=8) 1h after LPS were considered experimental group. Evaluation by auditory brainstem response (ABR) measurement, cochlear blood flow, and blood-labyrinth barrier (BLB) permeability were performed. Cochlear hair cells were observed by field emission-scanning electron microscopy (FE-SEM). MMP-9 activation was measured by gelatin zymography. RESULTS: For HUVEC, the tube formation was suppressed in a dose dependant manner. ALH-L1005 inhibited the MMP-9 activity prominently. It also attenuated the elevation of LPS-induced hearing threshold shift and recovery of CBF. By FE-SEM, cochlear hair cells could be preserved in experimental group. ALH-L1005 significantly reduced the BLB opening compared to LPS group. Active MMP-9 expression could be detected in the LPS group. In contrast to ALH-L1005 group, active MMP-9 expression was not detected. CONCLUSION: Our results conclude that ALH-L1005 showed a protective effect in the cochlear lateral wall damage induced by LPS.

Effect of ginkgo biloba extract on recovery after facial nerve crush injury in the rat.

BACKGROUND AND OBJECTIVE: Many pharmacological agents have shown successful results in experimental crush injury of the peripheral nerve. To date, therapeutic effect of ginkgo biloba extract (GBE) on the peripheral nerve crush injury of rats has been rarely reported, moreover, neuroprotective effect on the facial nerve crush injury has not been reported. MATERIALS AND METHODS: Prospective functional recovery, using a vibrissae movement and electrophysiological analysis of recovery 4 weeks after the facial nerve crush in adult rats, and comparison with randomized intraperitoneal injection of either GBE or control phosphate buffered saline. RESULTS: Relative to the control group (26 days post operation), administration of GBE significantly accelerated the recovery of vibrissae orientation to 11.7 days post the operation. A significant functional recovery was observed by postoperative 2nd week in the experimental group. The recovery of threshold and conduction velocity, postoperative 4th week in the experimental group, showed statistically significant difference compared to that of the control group. CONCLUSION: From this result, intraperitoneal injection of GBE has been found effective in promoting the regeneration of the nerve in an experimental facial nerve crush rat model. Further studies, including morphological and molecular analyses, are necessary to clarify the mechanisms of GBE on the facial nerve crush.

Effect of Ginkgo biloba extract on endotoxin-induced labyrinthitis.

OBJECTIVE: There are no reports on the therapeutic effect of Ginkgo biloba extract (GBE) on otitis media-induced labyrinthitis. The present study examined whether GBE can protect against cochlear damage induced by intratympanic instillation of lipopolysaccharide (LPS)-induced labyrinthitis. MATERIALS AND METHODS: Experiments were performed in 20 healthy young male guinea pigs. The control group (n=10) received an intratympanic instillation of LPS (20 µl, 3mg/ml). The experimental group (n=10) received intratympanic instillation of LPS immediately after instillation of GBE (10mg/kg) and then experimental groups received GBE (100mg/kg) by intraperitoneal injection every day for 3 days. Instillation of LPS or LPS immediately after GBE was done in the right ear; the untreated left ear was considered normal. Physiological and morphological changes were evaluated. RESULTS: Statistical analysis of treatment of GBE revealed significantly less hearing loss than LPS group (p<0.05). The ratio of the value of cochlear blood flow (CBF) compared to untreated left side was significantly higher in the GBE treated group than in the LPS-treated group (p<0.05). This result indicated the recovery of CBF in GBE treated group compared to LPS treated group. In the LPS group, scanning electron microscopy revealed hair cell damage with edema. Missing stereocilia in the third layer of the outer hair cell was revealed. However, both the inner hair cells and the outer hair cells had normal appearance in the GBE group. LPS group showed that cochlear Evans blue extravasation was increased strongly in the stria vascularis, spiral limbus, and in the spiral ligament compared with the GBE treated group. CONCLUSION: GBE significantly minimizes cochlear damage against LPS-induced otitis media with labyrinthitis in a guinea pig model. GBE has potential as an adjunctive therapy to antibiotics in the treatment of acute otitis media with complicated labyrinthitis.

Antibacterial effect of octylcyanoacrylate against methicillin-resistant Staphylococcus aureus isolates from patients with chronic suppurative otitis media.

UNLABELLED: There has been a steady increase in the number of cases of methicillin-resistant Staphylococcus aureus (MRSA) otorrhea; this is a growing medical concern. For otological surgery in children, octylcyanoacrylate can be an alternative method of closure for surgical incisions. Recent in vitro studies have shown that octylcyanoacrylate is effective as an antimicrobical barrier. To date, there have been only rare reports on the antibacterial effect of octylcyanoacrylate against MRSA. The purpose of this study is to determine the antimicrobial effects of octylcyanoacrylate against the MRSA that was isolated from patients with chronic suppurative otitis media. MATERIALS AND METHODS: Clinical MRSA (n=20) bacteria and methicillin-sensitive SA (MSSA) (n=20) were obtained from patients. The susceptibilities to various antibiotics were determined by disk diffusion method. RESULTS: MSSA was sensitive to octylcyanoacrylate. The antibacterial activity of octylcyanoacrylate was weak against MRSA. CONCLUSION: Our results demonstrated that octylcyanoacrylate has slight antibacterial activity against MRSA.

Antibacterial effect of tea-tree oil on methicillin-resistant Staphylococcus aureus biofilm formation of the tympanostomy tube: an in vitro study.

UNLABELLED: The antibacterial effects of tea-tree oil against the formation of methicillin-resistant Staphylococcus aureus (MRSA) biofilm on the surface of the tympanostomy tubes was evaluated. MATERIALS AND METHODS: Silicone tympanostomy tubes were pretreated with normal saline for 12 hours, the control group (n=4), with 100% tea-tree oil, experimental group A (n=3), or with 50% tea-tree oil, experimental group B (n=3). All the tubes were incubated in a MRSA solution for 2 days and then processed for evaluation using scanning electron microscopy. RESULTS: The development of the biofilm mode of growth of MRSA was observed in the saline-treated control group. In contrast, only focal biofilms were present on the tube surface in experimental group A and considerable reduction of biofilm with destruction of the MRSA cells was shown in experimental group B. CONCLUSION: From these results, the antimicrobial effect of tea-tree oil against biofilm formation on tympanostomy tubes in vitro has been verified.

Anti-allergic effects of Artemisia iwayomogi on mast cell-mediated allergy model.

The discovery of drugs for the treatment of allergic disease is an important subject in human health. The Artemisia iwayomogi (Compositae) (AIE) has been used as a traditional medicine in Korea and is known to have an anti-inflammatory effect. However, its specific mechanism of action is still unknown. In this report, we investigated the effect of AIE on the mast cell-mediated allergy model and studied the possible mechanism of action. AIE inhibited compound 48/80-induced systemic reactions and plasma histamine release in mice. AIE decreased immunoglobulin E (IgE)-mediated local allergic reaction, passive cutaneous anaphylaxis (PCA) reaction. AIE dose dependently attenuated histamine release from rat peritoneal mast cells activated by compound 48/80 or IgE. AIE decreased the compound 48/80-induced intracellular Ca(2+). Furthermore, AIE decreased the phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated tumor necrosis factor-alpha and interleukin-6 gene expression and production in human mast cells. The inhibitory effect of AIE on the proinflammatory cytokine was p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) dependent. AIE attenuated PMA plus A23187-induced degradation of IkappaBalpha and nuclear translocation of NF-kappaB and specifically blocked activation of p38 MAPK but not that of c-jun N-terminal kinase and extracellular signal-regulated kinase. Our findings provide evidence that AIE inhibits mast cell-derived immediate-type allergic reactions and involvement of intracellular Ca(2+), proinflammatory cytokines, p38 MAPK, and NF-kappaB in these effects.

Isodon japonicus decreases immediate-type allergic reaction and tumor necrosis factor-alpha production.

BACKGROUND: The immediate-type allergic reaction is involved in many allergic diseases such as asthma, allergic rhinitis and sinusitis. The discovery of drugs for the treatment of immediate-type allergic disease is a very important subject in human health. Isodon japonicus Hara (Labiatae) (IJAE) has been used for centuries as a traditional medicine in Korea and is known to have an anti-inflammatory effect. However, its specific mechanism of action is still unknown. In this report, we investigated the effect of IJAE on the immediate-type allergic reaction and studied its possible mechanisms of action, focusing on the mast cell-mediated allergic reaction. METHODS: IJAE extracts were anally administered to mice for high and fast absorption. Compound 48/80-induced mortality and compound 48/80- or immunoglobulin E (IgE)-induced histamine release were measured to evaluate the antiallergic effects of IJAE. The effect of IJAE on the model of local allergic reaction in vivo, passive cutaneous anaphylaxis (PCA), was investigated. The production of tumor necrosis factor-alpha (TNF-alpha) was measured by Western blotting. RESULTS: IJAE inhibited compound 48/80-induced systemic reactions and plasma histamine release in mice. IJAE decreased the PCA reaction activated by anti-dinitrophenyl (DNP) IgE antibody. IJAE dose-dependently reduced histamine release from rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE. Furthermore, IJAE decreased the production of TNF-alpha in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated human mast cells. CONCLUSION: Our findings provide evidence that IJAE inhibits mast cell-derived immediate-type allergic reactions, and also demonstrate the involvement of TNF-alpha in these effects. We propose the clinical use of IJAE in mast cell-mediated immediate-type allergic diseases.

Anti-oxidant adaptation in the AML cells supersensitive to hydrogen peroxide.

The purpose of this study was to investigate the adaptive mechanisms of hydrogen peroxide-supersensitive AML cells against the reactive oxygen species (ROS). Their scavenging capacity against ROS was determined using a fluorometric probe in the doxorubicin-resistant AML-2/DX100 cell characterized by the down-regulation of catalase. AML-2/DX100 cells had more scavenging capacity against endogenous pro-oxidants than did the parental cells AML-2/WT, suggesting that an anti-oxidant adaptation against ROS occurred. cDNA microarrays for 8000 human genes revealed that among 21 anti-oxidant genes, each four gene was up- and down-regulated more than 1.5-fold in AML-2/DX100 compared with AML-2/WT. The mRNA expression of glutathione S-transferase Pi, peroxiredoxin 2, thioredoxin 2, and glutaredoxin was elevated whereas that of peroxiredoxin 3, metallothionein-1F, superoxide dismutase 2, and thioredoxin reductase 1 was depressed. The result indicates that the down-regulation of certain anti-oxidant mechanisms can be compensated for by the up- and down-regulation of the other anti-oxidant mechanisms.

Reversal of P-glycoprotein-mediated multidrug resistance by protopanaxatriol ginsenosides from Korean red ginseng.

The overexpression of P-glycoprotein (Pgp) or the multidrug resistance-associated protein (MRP) confers multidrug resistance (MDR) to cancer cells. MDR cells can be sensitized to anticancer drugs when treated concomitantly with an MDR modulator. In this study, we investigated whether or not ginseng saponins could reverse MDR mediated by Pgp or MRP. The chemosensitization and drug accumulation effects of ginseng saponins such as the total saponin, protopanaxadiol ginsenosides (PDG), protopanaxatriol ginsenosides (PTG), ginsenosides-Rb 1, -Rb 2, -Rc, -Rg 1 and -Re were tested on the daunorubicin- and doxorubicin-resistant acute myelogenous leukemia sublines (AML-2/D100 and AML-2/DX100), which overexpress Pgp and MRP, respectively. PTG showed cytotoxicity in both sublines and was able to reverse resistance in the AML-2/D100 subline in a concentration-dependent manner. Conversely, other ginseng saponins at concentrations less than 300 microg/mL showed neither cytotoxicity nor chemosensitizing activity in both resistant sublines. Flow cytometry analysis showed that the effect of PTG (100 microg/mL) on drug accumulation of daunorubicin in the AML-2/D100 subline was 2-fold higher than that observed in the presence of verapamil (5 microg/mL) and 1.5 times less than cyclosporin A (3 microg/mL). The maximum non-cytotoxic concentrations of PTG did not appear to increase the Pgp levels, which is in contrast to verapamil and cyclosporin A. PTG at 200 microg/mL or more completely inhibited the azidopine photolabeling of Pgp. The results suggest that PTG has a chemosensitizing effect on Pgp-mediated MDR cells by increasing the intracellular accumulation of drugs through direct interaction with Pgp at the azidopine site. In addition, PTG may have a beneficial effect on cancer chemotherapy with respect to the possibility of long-term use without the concern of Pgp activation.